tbuckley/cabot-search huggingface dataset:
Transformative learning for a sustainable and healthy future through ecosystem approaches to health: insights from 15 years of co-designed ecohealth teaching and learning experiences
Authors: Jena Webb, Sergio Raez-Villanueva, Paul D Carrière, Audrey-Anne Beauchamp, Isaac Bell, Angela Day, Sarah Elton, Mathieu Feagan, Jolene Giacinti, Jean Paul Kabemba Lukusa, Celia Kingsbury, Paola A Torres-Slimming, Martin Bunch, Katie Clow, Maya K Gislason, Margot W Parkes, E Jane Parmley, Blake Poland, Cathy Vaillancourt
Journal: The Lancet Planetary Health (2023)

This paper presents insights from the work of the Canadian Community of Practice in Ecosystem Approaches to Health (CoPEH-Canada) and 15 years (2008–2022) of land-based, transdisciplinary, learner-centred, transformative learning and training. We have oriented our learning approaches to Head, Hands, and Heart, which symbolise cognitive, psychomotor, and affective learning, respectively. Psychomotor and affective learning are necessary to grapple with and enact far-reaching structural changes (eg, decolonisation) needed to rekindle healthier, reciprocal relationships with nature and each other. We acknowledge that these approaches have been long understood by Indigenous colleagues and communities. We have developed a suite of teaching techniques and resources through an iterative and evolving pedagogy based on participatory approaches and operating reciprocal, research-pedagogical cycles; integrated different approaches and ways of knowing into our pedagogy; and built a networked Community of Practice for continued learning. Planetary health has become a dominant framing for health-ecosystem interactions. This Viewpoint underscores the depth of existing scholarship, collaboration, and pedagogical expertise in ecohealth teaching and learning that can inform planetary health education approaches.
The Planetary Health Academy—a virtual lecture series for transformative education in Germany
Authors: Sophie Gepp, Laura Jung, Katharina Wabnitz, Frederick Schneider, Friederike v Gierke, Hannah Otto, Sylvia Hartmann, Theresa Gemke, Christian Schulz, Sabine Gabrysch, Marischa Fast, Eva-Maria Schwienhorst-Stich
Journal: The Lancet Planetary Health (2023)

The planetary crises require health professionals to understand the interlinkages between health and environmental changes, and how to reduce ecological harm (ie, ecological footprint) and promote positive change (ie, ecological handprint). However, health professions' education and training are mostly lacking these aspects. In this Viewpoint, we report findings from the evaluation of the Planetary Health Academy, the first open online lecture series for transformative planetary health education in Germany. In a retrospective online survey, 458 of 3656 Planetary Health Academy participants reported on their emotions towards climate change, attitudes towards health professionals' responsibilities, self-efficacy, and the contribution of the Planetary Health Academy to their knowledge and actions. Additionally, motivators and barriers to acting were assessed. Our findings provide insights that can inform future efforts for transformative education. Combined with network and movement building, education could act as a social tipping element toward actions to mitigate global environmental changes.
Who should be screened for post-partum cardiovascular risk?
Authors: Graeme N Smith, Jessica Pudwell
Journal: The Lancet Healthy Longevity (2023)

The association between pre-eclampsia and risk of cardiovascular disease and cardiovascular death was first reported in the early 2000s.1 Since then, many studies have identified that pre-eclampsia with severe features, including preterm birth, fetal growth restriction, severe hypertension, and recurrence in subsequent pregnancies, further compounds that risk. Independently of pre-eclampsia, other pregnancy complications (ie, gestational hypertension, gestational diabetes, idiopathic preterm birth, fetal growth restriction, and placental abruption) have also been linked to underlying cardiovascular risk factors and increased risk of future cardiovascular disease.
DGKB mediates radioresistance by regulating DGAT1-dependent lipotoxicity in glioblastoma
Authors: Hyunkoo Kang, Haksoo Lee, Kyeongmin Kim, Eunguk Shin, Byeongsoo Kim, JiHoon Kang, Bohkyung Kim, Jung Sub Lee, Jae-Myung Lee, HyeSook Youn, BuHyun Youn
Journal: Cell Reports Medicine (2023)

Glioblastoma (GBM) currently has a dismal prognosis. GBM cells that survive radiotherapy contribute to tumor progression and recurrence with metabolic advantages. Here, we show that diacylglycerol kinase B (DGKB), a regulator of the intracellular concentration of diacylglycerol (DAG), is significantly downregulated in radioresistant GBM cells. The downregulation of DGKB increases DAG accumulation and decreases fatty acid oxidation, contributing to radioresistance by reducing mitochondrial lipotoxicity. Diacylglycerol acyltransferase 1 (DGAT1), which catalyzes the formation of triglycerides from DAG, is increased after ionizing radiation. Genetic inhibition of DGAT1 using short hairpin RNA (shRNA) or microRNA-3918 (miR-3918) mimic suppresses radioresistance. We discover that cladribine, a clinical drug, activates DGKB, inhibits DGAT1, and sensitizes GBM cells to radiotherapy in vitro and in vivo. Together, our study demonstrates that DGKB downregulation and DGAT1 upregulation confer radioresistance by reducing mitochondrial lipotoxicity and suggests DGKB and DGAT1 as therapeutic targets to overcome GBM radioresistance.
Cardiovascular mortality in women in their forties after hypertensive disorders of pregnancy in the Netherlands: a national cohort study
Authors: Sophie M Welters, Marjon de Boer, Pim W Teunissen, Wietske Hermes, Anita C J Ravelli, Ben W Mol, Christianne J M de Groot
Journal: The Lancet Healthy Longevity (2023)

Hypertensive disorders of pregnancy are associated with cardiovascular disease later in life. Given that hypertensive disorders of pregnancy often occur at a relatively young age, there might be an opportunity to use preventive measures to reduce the risk of early cardiovascular disease and mortality. The aim of this study was to assess the risk of cardiovascular mortality in women after a hypertensive disorder of pregnancy.
Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases
Authors: Jiawei Guo, Fuxiao Wang, Yan Hu, Ying Luo, Yan Wei, Ke Xu, Hao Zhang, Han Liu, Lumin Bo, Shunli Lv, Shihao Sheng, Xinchen Zhuang, Tao Zhang, Can Xu, Xiao Chen, Jiacan Su
Journal: Cell Reports Medicine (2023)

Systematic bone loss is commonly complicated with inflammatory bowel diseases (IBDs) with unclear pathogenesis and uncertain treatment. In experimental colitis mouse models established by dextran sulfate sodium and IL-10 knockout induced with piroxicam, bone mass and quality are significantly decreased. Colitis mice demonstrate a lower bone formation rate and fewer osteoblasts in femur. Bone marrow mesenchymal stem/stromal cells (BMSCs) from colitis mice tend to differentiate into adipocytes rather than osteoblasts. Serum from patients with IBD promotes adipogenesis of human BMSCs. RNA sequencing reveals that colitis downregulates Wnt signaling in BMSCs. For treatment, exosomes with Golgi glycoprotein 1 inserted could carry Wnt agonist 1 and accumulate in bone via intravenous administration. They could alleviate bone loss, promote bone formation, and accelerate fracture healing in colitis mice. Collectively, BMSC commitment in inflammatory microenvironment contributes to lower bone quantity and quality and could be rescued by redirecting differentiation toward osteoblasts through bone-targeted drug delivery.
LAMC2 Regulates Key Transcriptional and Targetable Effectors to Support Pancreatic Cancer Growth
Authors: Oihane Erice, Shruthi Narayanan, Iker Feliu, Rodrigo Entrialgo-Cadierno, Antonia Malinova, Caterina Vicentini, Elizabeth Guruceaga, Pietro Delfino, Marija Trajkovic-Arsic, Haritz Moreno, Karmele Valencia, Ester Blanco, Irati Macaya, Daniel Öhlund, Purvesh Khatri, Fernando Lecanda, Aldo Scarpa, Jens T. Siveke, Vincenzo Corbo, Mariano Ponz-Sarvise, Silve Vicent
Journal: Clinical Cancer Research (2023)

The identification of pancreatic ductal adenocarcinoma (PDAC) dysregulated genes may unveil novel molecular targets entering inhibitory strategies. Laminins are emerging as potential targets in PDAC given their role as diagnostic and prognostic markers. Here, we investigated the cellular, functional, and clinical relevance of LAMC2 and its regulated network, with the ultimate goal of identifying potential therapies.LAMC2 expression was analyzed in PDAC tissues, a panel of human and mouse cell lines, and a genetically engineered mouse model. Genetic perturbation in 2D, 3D, and in vivo allograft and xenograft models was done. Expression profiling of a LAMC2 network was performed by RNA-sequencing, and publicly available gene expression datasets from experimental and clinical studies examined to query its human relevance. Dual inhibition of pharmacologically targetable LAMC2-regulated effectors was investigated.LAMC2 was consistently upregulated in human and mouse experimental models as well as in human PDAC specimens, and associated with tumor grade and survival. LAMC2 inhibition impaired cell cycle, induced apoptosis, and sensitized PDAC to MEK1/2 inhibitors (MEK1/2i). A LAMC2-regulated network was featured in PDAC, including both classical and quasi-mesenchymal subtypes, and contained downstream effectors transcriptionally shared by the KRAS signaling pathway. LAMC2 regulated a functional FOSL1-AXL axis via AKT phosphorylation. Furthermore, genetic LAMC2 or pharmacological AXL inhibition elicited a synergistic antiproliferative effect in combination with MEK1/2is that was consistent across 2D and 3D human and mouse PDAC models, including primary patient-derived organoids.LAMC2 is a molecular target in PDAC that regulates a transcriptional network that unveils a dual drug combination for cancer treatment.
Teaching skills for sustainable health care
Authors: Victoria Stanford, Stefi Barna, Dhruv Gupta, Frances Mortimer
Journal: The Lancet Planetary Health (2023)

In the context of accelerating concern regarding the climate and ecological crisis and the recognition of this crisis as a health threat, there is growing motivation among the health-care community to reduce the negative environmental impact of health care. Globally, the health-care sector is estimated to be the 5th largest carbon emitter. A health system that is socially, environmentally, and financially sustainable requires clinical leadership, yet few health-care workers possess the conceptual framework or practical skills for creating new models of care. Clinicians can protect planetary health as a core part of professional practice by integrating triple bottom line measures into quality improvement or quality management practices. Initial efforts to integrate sustainability into quality improvement teaching and training have been shown to transform learners' interest in quality improvement and environmental sustainability. Embedding sustainability principles and techniques into established quality improvement education and practice can operationalise planetary health, building the skills necessary for health-care system transformation at the speed and scale required.
Effects of a community gardening intervention on diet, physical activity, and anthropometry outcomes in the USA (CAPS): an observer-blind, randomised controlled trial
Authors: Jill S Litt, Katherine Alaimo, Kylie K Harrall, Richard F Hamman, James R Hébert, Thomas G Hurley, Jenn A Leiferman, Kaigang Li, Angel Villalobos, Eva Coringrato, Jimikaye Beck Courtney, Maya Payton, Deborah H Glueck
Journal: The Lancet Planetary Health (2023)
Antibiotic concentrations and antibiotic resistance in aquatic environments of the WHO Western Pacific and South-East Asia regions: a systematic review and probabilistic environmental hazard assessment
Authors: Nada Hanna, Ashok J Tamhankar, Cecilia Stålsby Lundborg
Journal: The Lancet Planetary Health (2023)

Antibiotic resistance poses human health risks, and there are concerns about the effect of environmental antibiotic residues in the selection and spread of antibiotic resistance. The aim of this study was to identify antibiotic residue levels that are likely to select for resistance and relative contributions from different aquatic sources, of various aquatic environmental compartments of the WHO Western Pacific region (WPR) and the WHO South-East Asia region (SEAR), including in China and India.A systematic review of empirical studies that measured antibiotic concentrations in aquatic environments, published between 2006 and 2019, and a probabilistic environmental hazard assessments approach, were used to identify antibiotic concentrations that are likely to select for resistance in various aquatic environmental compartments of the WPR and SEAR, including in China and India. The assessment involved the use of measured environmental concentrations and predicted no-effect concentrations (PNECs).The systematic review found 218 relevant studies of 5230 screened from the WPR and 22 relevant studies of 2625 screened from the SEAR; some of these relevant studies were largely from China (n=168) and India (n=15). 92 antibiotics in the WPR and 45 in the SEAR were detected in various aquatic compartments. Antibiotic concentrations that most likely exceeded PNECs (0-100%) were observed in wastewater, and influents and effluents of wastewater treatment plants. Antibiotic concentrations that most likely exceeded PNECs were also observed in aquatic environmental compartments. The highest risk for the development of resistance was in tap or drinking water of the WPR and China for ciprofloxacin (62·5%). The relative contributions of potential sources of antibiotic contamination in waterways, such as hospitals, municipals, livestock, and pharmaceutical manufacturing, was determined for each antibiotic.The concentrations of antibiotic residues found in wastewater and wastewater treatment plants of the WPR and SEAR make them potential hotspots for the development of antibiotic resistance, which creates human health risks from environmental exposure via drinking water. These findings can help decision makers to target risk reduction measures against environmental residues of priority antibiotics in high-risk sites, and help to focus research efforts in these world regions.Swedish Research Council.
Informative Censoring of Progression-Free Survival Data in the TROPiCS-02 Trial: An Unrecognized Bias
Authors: Guo-Fu Li, Yu-Wei Qiao, Ai-Jia Guan, Guo Yu
Journal: Journal of Clinical Oncology (2023)

Rugo et al 1 present the primary results of the TROPiCS-02, a global, randomized, phase III trial of sacituzumab govitecan versus single-agent chemotherapy and conclude that sacituzumab govitecan demonstrated a significant improvement in progression-free survival (PFS) over chemotherapy (hazard ratio, 0.66; 95% CI, 0.53 to 0.83; P 5 .0003).Of note, the conclusion must comply with the fundamental assumption of Kaplan-Meier analysis of noninformative censoring 2-4 ; however, we identify a potentially unrecognized bias of informative censoring associated significantly with Rugo et al's 1 PFS analysis (Fig 2A 1 ) using reconstructed deidentified individual participant data of the TROPiCS-02 trial.
Mental Health of Transgender and Gender Diverse Youth
Authors: Natalie M. Wittlin, Laura E. Kuper, Kristina R. Olson
Journal: Annual Review of Clinical Psychology (2023)

Transgender and gender diverse (TGD) children and adolescents are an increasingly visible yet highly stigmatized group. These youth experience more psychological distress than not only their cisgender, heterosexual peers but also their cisgender, sexual minority peers. In this review, we document these mental health disparities and discuss potential explanations for them using a minority stress framework. We also discuss factors that may increase and decrease TGD youth's vulnerability to psychological distress. Further, we review interventions, including gender-affirming medical care, that may improve mental health in TGD youth. We conclude by discussing limitations of current research and suggestions for the future.
Public Health Preparedness for Extreme Heat Events
Authors: Jeremy J. Hess, Nicole A. Errett, Glenn McGregor, Tania Busch Isaksen, Zachary S. Wettstein, Stefan K. Wheat, Kristie L. Ebi
Journal: Annual Review of Public Health (2023)

Heat is a dangerous hazard that causes acute heat illness, chronic disease exacerbations, adverse pregnancy outcomes, and a range of injuries. Risks are highest during extreme heat events (EHEs), which challenge the capacity of health systems and other critical infrastructure. EHEs are becoming more frequent and severe, and climate change is driving an increasing proportion of heat-related mortality, necessitating more investment in health protection. Climate-resilient health systems are better positioned for EHEs, and EHE preparedness is a form of disaster risk reduction. Preparedness activities commonly take the form of heat action plans (HAPs), with many examples at various administrative scales. HAP activities can be divided into primary prevention, most important in the pre-event phase; secondary prevention, key to risk reduction early in an EHE;and tertiary prevention, important later in the event phase. After-action reports and other postevent evaluation activities are central to adaptive management of this climate-sensitive hazard.
When I use a word . . . . Medical anniversaries in 2023
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

My list of 66 medically related anniversaries for 2023 (events in years ending '23 and'73) includes: ● foundation of the Chelsea Physic Garden (1673); ● foundation of The Lancet by Thomas Wakley (October 1823); ● Roe v Wade (1973); ● Twenty five births include: Hans Berger, German neurologist; Aimé Bonpland, French physician and botanist; Alexis Carrel, French surgeon and Nobel prize winner; Lloyd Conover, American pharmaceutical chemist; Félix d'Herelle, French-Canadian microbiologist; Théodore de Mayerne, Swiss physician; Carl Djerassi, American pharmaceutical chemist and novelist; Sigismund Elsholtz, German physician, botanist, and alchemist; Daniel Gajdusek, American virologist; Beatrix Hamburg, American psychiatrist; Richard Mead, English physician; Arthur Jensen, American educational psychologist; Otto Loewi, German pharmacologist; Georg Balthasar Metzger, German physician and scientist; William P Murphy Jr, American physician and inventor of medical devices; William Petty, English physician and political economist; Arnold S Relman, American physician and editor; Caspar Schamberger, German surgeon; Giovanni Antonio Scopoli, Italian physician and scientist; Ludwik Teichmann, Polish physician and anatomist; Alfred Russell Wallace, English naturalist; and Thomas Young, English scientist and polymath; ● Thirteen deaths include: Francis Anthony, English apothecary, physician, and alchemist; Matthew Baillie, Scottish physician and pathologist; John Caius, English physician; Regnier De Graaf, Dutch physician, physiologist, and anatomist; Walter Rudolf Hess, Swiss physiologist; Edward Jenner, English physician; Dickinson W Richards, American physician; Wilhelm Röntgen, German physicist; Antony van Leeuwenhoek, Dutch microscopist; Justus von Liebig, German chemist; and Selman Waksman, Ukrainian-American biochemist; ● Eleven biomedical texts published, written by Avicenna, Persian physician, astronomer, and philosopher; Gaspard Bauhin, Swiss botanist; William Budd, English physician; Aleixeu de Abreu, Portuguese physician and tropical pathologist; John Lelamour, English schoolmaster; Lucretius, Roman poet and philosopher; Marcello Malpighi, Italian physician; Girolamo Mercuriale, Italian physician; Raymond Pearl, American biologist; Costanzo Varolio, Italian anatomist and physician; Charles White, English physician; and Wilhelm Wundt, German physiologist; ● compilation of the Lelamour Herbal by John Lelamour, English schoolmaster (1373); ● anatomical, biochemical, haematological, microbiological, and physiological observations by Gasparus Aselli, Italian physician; Gerhard Henrik Armauer Hansen, Norwegian physician; William Prout, English chemist, physician, and theologian; Gaston Ramon, French biologist; Hilaire-Marin Rouelle, French chemist; and Antony van Leeuwenhoek, Dutch microscopist; ● Foundation of the pharmaceutical companies Novo Nordisk in Denmark (1923) and Sanofi in France (1973); ● Nobel prizes awarded to Banting and Macleod (1923) and to von Frisch, Lorenz, and Tinbergen (1973).
Associations between punitive policies and legal barriers to consensual same-sex sexual acts and HIV among gay men and other men who have sex with men in sub-Saharan Africa: a multicountry, respondent-driven sampling survey
Authors: Carrie E Lyons, Jean Olivier Twahirwa Rwema, Keletso Makofane, Daouda Diouf, Iliassou Mfochive Njindam, Ibrahima Ba, Abo Kouame, Ubald Tamoufe, Bai Cham, Mamadú Aliu Djaló, Evelyne-Patrice Obodou, Etienne Karita, Anato Simplice, Rebecca G Nowak, Trevor A Crowell, Sindy Matse, Seni Kouanda, Jean-Paul Enama, Matthew Kavanagh, Gregorio A Millett, Chris Beyrer, Sarah Murray, Stefan Baral
Journal: The Lancet HIV (2023)
Relaxation of anti-COVID-19 measures reveals new challenges for infectious disease outbreak forecasting
Authors: Oliver J Brady, Barbara Hofmann, Felipe J Colón-González, Rory Gibb, Rachel Lowe, Gina Tsarouchi, Quillon Harpham, Darren Lumbroso, Phan Trong Lan, Vu Sinh Nam
Journal: The Lancet Infectious Diseases (2023)
Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Eve Rodler, Priyanka Sharma, William E Barlow, Julie R Gralow, Shannon L Puhalla, Carey K Anders, Lori Goldstein, Debu Tripathy, Ursa A Brown-Glaberman, Thu-Tam Huynh, Christopher S Szyarto, Andrew K Godwin, Harsh B Pathak, Elizabeth M Swisher, Marc R Radke, Kirsten M Timms, Danika L Lew, Jieling Miao, Lajos Pusztai, Daniel F Hayes, Gabriel N Hortobagyi
Journal: The Lancet Oncology (2023)
Insulin degludec versus insulin detemir, both in combination with insulin aspart, in the treatment of pregnant women with type 1 diabetes (EXPECT): an open‑label, multinational, randomised, controlled, non-inferiority trial
Authors: Elisabeth R Mathiesen, Amra Ciric Alibegovic, Rosa Corcoy, Fidelma Dunne, Denice S Feig, Moshe Hod, Ting Jia, Balamurali Kalyanam, Soumitra Kar, Alexandra Kautzky-Willer, Cassio Marchesini, Rustam D Rea, Peter Damm
Journal: The Lancet Diabetes & Endocrinology (2023)